PROJECT SUMMARY/ABSTRACT Nearly half of the 61 million women of reproductive age (15-44 years) in the United States are overweight or obese, placing them and their offspring at elevated risk for adverse health outcomes. Notably, 15-20% of reproductive-age women use combined hormonal contraceptives (CHCs), including the combined estrogen and progestin oral pill, transdermal patch, or vaginal ring. While studies to date have not demonstrated a conclusive link between CHCs and weight gain, no studies have evaluated the impact of CHCs on weight loss in women with overweight/obesity who are actively trying to lose weight. Preliminary data suggests that CHC use may adversely impact weight loss within a behavioral weight loss program, with CHCs users losing 6 kg less than non-users. The overall objective of this mentored F32 proposal is to evaluate the impact of CHC use on weight loss, dietary adherence, and physical activity (PA) adherence in pre-menopausal women with overweight/obesity enrolled in an ongoing behavioral weight loss trial (R01 DK111622). The overall hypothesis is that CHC use will be associated with reduced adherence to diet and lower weight loss at 1 year, but no difference in adherence to PA. In Aim 1, changes in body weight and composition will be compared between CHC users and non-users. In Aim 2, adherence to diet and PA will be compared between groups using objective measures of these parameters. In Exploratory Aim 3, we will evaluate the impact of CHC use on eating behaviors, hormones related to hunger and satiety, stool microbiota, and components of energy expenditure (EE). The applicant, Adnin Zaman MD, is currently a third year endocrinology fellow whose long-term goal is to establish a research career at the interface of women?s health and obesity medicine, and to develop more effective obesity treatments for reproductive-aged women. To build upon her previous research experience and develop a line of research distinct from that of her mentor, Dr. Zaman and her mentorship team have developed a comprehensive training plan. The primary training objectives include 1) gaining further experience with weight loss interventional trials, 2) developing research skills in the assessment of free-living energy intake and eating behaviors, 3) developing research skills in the assessment of free-living EE and PA, 4) expanding knowledge base in the impact of reproductive hormones on energy balance, 5) evaluating the impact of CHC use on gut microbiome, 6) enhancing skills in quantitative data analysis and statistics, and 7) maturing professional development skills, grantsmanship, and publication productivity. This research and training will take place under the guidance of an experienced mentorship team at the University of Colorado Anschutz Medical Campus ? an environment that will provide Dr. Zaman exceptional opportunities to gain valuable skills and expertise. Successful completion of this proposal will result in several first-authored publications and will generate critical preliminary data needed to support a competitive K23 application. This F32 proposal will serve as both a superb training opportunity and as an original and meaningful scientific contribution to launch Dr. Zaman?s career as an academic physician-scientist.